Wildtype p53-specific Antibody and T-Cell Responses in Cancer Patients
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Wildtype p53-specific Antibody and T-Cell Responses in Cancer Patients. / Pedersen, Anders Elm; Stryhn, Anette; Justesen, Sune; Harndahl, Mikkel; Rasmussen, Susanne; Donskov, Frede; Claesson, Mogens H; Pedersen, Johannes W; Wandall, Hans H; Svane, Inge Marie; Buus, Søren.
I: Journal of Immunotherapy, Bind 34, Nr. 9, 2011, s. 629-40.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Wildtype p53-specific Antibody and T-Cell Responses in Cancer Patients
AU - Pedersen, Anders Elm
AU - Stryhn, Anette
AU - Justesen, Sune
AU - Harndahl, Mikkel
AU - Rasmussen, Susanne
AU - Donskov, Frede
AU - Claesson, Mogens H
AU - Pedersen, Johannes W
AU - Wandall, Hans H
AU - Svane, Inge Marie
AU - Buus, Søren
PY - 2011
Y1 - 2011
N2 - Mutation in the p53 gene based on single amino acid substitutions is a frequent event in human cancer. Accumulated mutant p53 protein is released to antigen presenting cells of the immune system and anti-p53 immune responses even against wt p53 is induced and observed in a number of human cancer patients. Detection of antibodies against wt p53 protein has been used as a diagnostic and prognostic marker and discovery of new T-cell epitopes has enabled design of cancer vaccination protocols with promising results. Here, we identified wt p53-specific antibodies in various cancer patients and identified a broad range of responses against wt p53 protein and 15-mer peptides using a novel print array technology. Likewise, using bioinformatic tools in silico, we identified CD8 T-cell specificity or reactivity against HLA-A*02:01 binding peptides wt p53(65-73), wt p53(187-197), and wt p53(264-272) in breast cancer patients and against HLA-A*01:01 binding peptide wt p53(226-234) and HLA-B*07:02 binding peptide wt p53(74-82) in renal cell cancer and breast cancer patients, respectively. Finally, we analyzed antibody and T-cell responses against wt p53 15-mer peptides in patients with metastatic renal cell carcinoma who were alive with no evidence of disease after a follow-up period of minimum 5 years after treatment with IL-2±IFN-a±histamine containing immunotherapy to identify novel epitopes for use in immunotherapy and for potential response biomarkers. However, none of the wt p53 reactivity observed justified use of 15-mer or was related to survival in this rare patient population.
AB - Mutation in the p53 gene based on single amino acid substitutions is a frequent event in human cancer. Accumulated mutant p53 protein is released to antigen presenting cells of the immune system and anti-p53 immune responses even against wt p53 is induced and observed in a number of human cancer patients. Detection of antibodies against wt p53 protein has been used as a diagnostic and prognostic marker and discovery of new T-cell epitopes has enabled design of cancer vaccination protocols with promising results. Here, we identified wt p53-specific antibodies in various cancer patients and identified a broad range of responses against wt p53 protein and 15-mer peptides using a novel print array technology. Likewise, using bioinformatic tools in silico, we identified CD8 T-cell specificity or reactivity against HLA-A*02:01 binding peptides wt p53(65-73), wt p53(187-197), and wt p53(264-272) in breast cancer patients and against HLA-A*01:01 binding peptide wt p53(226-234) and HLA-B*07:02 binding peptide wt p53(74-82) in renal cell cancer and breast cancer patients, respectively. Finally, we analyzed antibody and T-cell responses against wt p53 15-mer peptides in patients with metastatic renal cell carcinoma who were alive with no evidence of disease after a follow-up period of minimum 5 years after treatment with IL-2±IFN-a±histamine containing immunotherapy to identify novel epitopes for use in immunotherapy and for potential response biomarkers. However, none of the wt p53 reactivity observed justified use of 15-mer or was related to survival in this rare patient population.
U2 - 10.1097/CJI.0b013e3182281381
DO - 10.1097/CJI.0b013e3182281381
M3 - Journal article
C2 - 21989411
VL - 34
SP - 629
EP - 640
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1524-9557
IS - 9
ER -
ID: 35076833